Department of Psychiatry, Alfred Health, Melbourne, Victoria, Australia.
Neuropsychiatry Centre, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Epilepsia. 2024 Sep;65(9):2751-2763. doi: 10.1111/epi.18065. Epub 2024 Jul 20.
Research suggests that recurrent seizures may lead to neuronal injury. Neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAP) levels increase in cerebrospinal fluid and blood in response to neuroaxonal damage, and they have been hypothesized as potential biomarkers for epilepsy. We examined plasma NfL and GFAP levels and their diagnostic utility in differentiating patients with epilepsy from those with psychogenic nonepileptic seizures (PNES) and other nonepileptic disorders.
We recruited consecutive adults admitted for video-electroencephalographic monitoring and formal neuropsychiatric assessment. NfL and GFAP levels were quantified and compared between different patient groups and an age-matched reference cohort (n = 1926) and correlated with clinical variables in patients with epilepsy.
A total of 138 patients were included, of whom 104 were diagnosed with epilepsy, 22 with PNES, and 12 with other conditions. Plasma NfL and GFAP levels were elevated in patients with epilepsy compared to PNES, adjusted for age and sex (NfL p = .04, GFAP p = .04). A high proportion of patients with epilepsy (20%) had NfL levels above the 95th age-matched percentile compared to the reference cohort (5%). NfL levels above the 95th percentile of the reference cohort had a 95% positive predictive value for epilepsy. Patients with epilepsy who had NfL levels above the 95th percentile were younger than those with lower levels (37.5 vs. 43.8 years, p = .03).
An elevated NfL or GFAP level in an individual patient may support an underlying epilepsy diagnosis, particularly in younger adults, and cautions against a diagnosis of PNES alone. Further examination of the association between NfL and GFAP levels and specific epilepsy subtypes or seizure characteristics may provide valuable insights into disease heterogeneity and contribute to the refinement of diagnosis, understanding pathophysiological mechanisms, and formulating treatment approaches.
研究表明，反复发作的癫痫可能导致神经元损伤。神经丝轻链蛋白（NfL）和胶质纤维酸性蛋白（GFAP）在脑脊液和血液中的水平会因神经轴突损伤而升高，它们被假设为癫痫的潜在生物标志物。我们检测了血浆 NfL 和 GFAP 水平，并研究了它们在区分癫痫患者与非癫痫性精神障碍（PNES）和其他非癫痫性疾病患者中的诊断效用。
我们连续招募了因视频-脑电图监测和正式神经精神评估而入院的成年患者。在不同的患者组和年龄匹配的参考队列（n=1926）之间定量比较 NfL 和 GFAP 水平，并与癫痫患者的临床变量相关联。
共纳入 138 例患者，其中 104 例诊断为癫痫，22 例为 PNES，12 例为其他疾病。与 PNES 相比，癫痫患者的血浆 NfL 和 GFAP 水平升高，调整年龄和性别后（NfL p=0.04，GFAP p=0.04）。与参考队列（5%）相比，癫痫患者中有相当比例（20%）的 NfL 水平高于第 95 个年龄匹配百分位。参考队列中 NfL 水平高于第 95 个百分位的阳性预测值为 95%。NfL 水平高于参考队列第 95 个百分位的癫痫患者比水平较低的患者年龄更小（37.5 岁 vs. 43.8 岁，p=0.03）。
个体患者的 NfL 或 GFAP 水平升高可能支持潜在的癫痫诊断，特别是在年轻成年人中，并且应避免仅凭 PNES 做出诊断。进一步研究 NfL 和 GFAP 水平与特定癫痫亚型或发作特征之间的关联可能会深入了解疾病异质性，并有助于改进诊断、理解病理生理机制和制定治疗方法。
